丘脑底核高频电刺激对偏侧帕金森猴苍白球内侧部中氨基酸神经递质含量的影响

目的通过微透析-高效液相神经递质分析技术观察丘脑底核(subthalamic nucleus,STN)脑深部电刺激(deep brain stimulation,DBS)对偏侧帕金森(parkinson’s disease,PD)模型猴苍白球内侧部(globus pallidusinternus,GPi)氨基酸类神经递质水平的影响。探讨PD的发病机制及DBS治疗PD的可能作用机制。方法成功制备的偏侧PD模型猴4只,微透析方法收集未注药侧GPi的细胞外液以及注药侧STN高频电刺激(highfrequncy stimulation,HFS)过程中以及刺激前后同侧GPi的细胞外液,应用高效液相-荧光法分析谷氨酸(gluta-mate,Glu)和γ-氨基丁酸(gamma-aminobutyric acid,GABA)的水平变化。结果 MPTP注药侧GPi细胞外液中Glu含量较未注药侧升高,而GABA含量却下降。高频电刺激偏侧PD猴模型的STN后,同侧的GPi细胞外液中Glu的含量明显上升,而GABA的含量无明显变化。结论无法用单一的神经元抑制机制解释STN-HFS的作用机制,STN-HFS的作用不只是局限于STN核团本身,对整个基底节环路都有影响。     

帕金森病人GPi、Vim及STN的电生理特性研究

目的　探讨帕金森病 (PD)患者的苍白球内侧部 (GPi) ,丘脑腹外侧中间核 (Vim)及丘脑底核 (STN)的电生理特性。方法　用立体定向毁损术治疗 54例PD手术中 ,应用美国FHC公司生产的微电极记录系统 ,记录GPi、Vim和STN不同部位的电活动。结果　PD病人的丘脑内和基底节不同结构部位的电活动频率、幅度、放电方式和背景噪声均有显著差异 ;Vim中可记录到与震颤同步的高频放电 ,GPi、STN可记录到一致稳定的放电活动。结论　利用GPi、Vim和STN不同部位的电活动特性 ,可以为立体定向治疗PD手术中的精确定位 ,提高疗效 ,降低并发症提供参考依据     

帕金森性震颤和与震颤相关的电活动

目的对PD患者行STN和GPi切开术术中应用微电极记录技术采集神经元的电活动,术后分析其与震颤的关系和特点,为手术选择最佳的毁损位置提供客观的电生理指标.方法40个PD患者,其中21例PD患者接受了立体定向GPi切开术和19例PD患者接受立体定向STN切开术.病人要求清醒合作且处于“关”状态.术中应用微电极和肌电(EMG)记录技术,采集GPi和STN神经元和手术对侧肢体震颤的生物电活动.术后应用分析软件甄别单细胞及其电活动特点,分析其与震颤症状的关系,并进行相关性检验.结果在21个针道共记录到184 GPi个神经元单位,其簇状放电的节律与肢体震颤的节律高度一致(4～6Hz),R2=0.78(P＜0.01).在20个针道共记录到161个STN神经元单位,其放电频率在42～88Hz之间.STN的簇状放电的节律与肢体震颤的节律一致(4～6Hz),R2=0.64(P＜0.01).毁损这些震颤细胞导致震颤症状的消失.结论震颤型PD患者的GPi和STN存在与肢体震颤节律一致的震颤细胞,且震颤和震颤细胞有着内在的关系.对于指导手术毁损的部位和范围提供了可靠的依据.     

帕金森病人GPi、Vim及STN的电生理特征研究

目的：探讨帕金森病（PD）患者的苍白球内侧部（GPi)，丘脑腹外侧中间核（Vim)及丘脑底核（STN）的电生理特性，方法：用立体定向毁损术治疗54例PD手术中，应用美国FHC公司生产的微电极记录系统，记录GPi,Vim和STN不同部位的电活动。结果PD病人的丘脑内和基底节不同结构部位怕电话动频率，幅度，放电 背景噪声均有显著差异，Vim中可记录到与震颤同步的高频放电，GPi，STN可记录到一致稳定的放电活动。结论：利用GPi,Vim和STN不同部位的电活动特性，可以为立体定向治疗PD手术中的精确定位，提高疗效，降低并发症提供参考依据。     

帕金森病猴丘脑底核神经元的电生理特性

目的探讨帕金森病(PD)猴模型丘脑底核(STN)神经元的电生理特性,为研究帕金森病的病理生理过程提供动物实验依据。方法应用颈内动脉注射MPTP建立PD猴模型。在立体定向仪引导下应用细胞外记录的方法记录"造模"前后猴病理及正常生理状态下STN神经元的放电活动,并对其放电模式进行分析。结果电生理记录显示STN神经元放电频率在生理状态下为2.03±1.12Hz;在病理状态下为9.58±0.85 Hz(P<0.01)。在生理状态下有20个(20/35,57.14%)神经元呈现簇发放电,有15个(15/35,42.86%)神经元呈现连续放电;在PD病理状态下有10个(10/12,85.71%)神经元呈现簇发放电,有2个(2/12,14.29%)神经元呈现连续放电(P<0.05)。生理状态下STN神经元的ISI序列散在分布于30～980ms之间;在PD病理状态下当STN神经元呈连续放电时,ISI分布于50～360ms之间,在150ms以下有一个分布密集条带,当STN神经元呈簇发放电时,ISI分布于30～470ms之间,在40ms以下有一个分布密集条带。结论PD猴模型STN神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大,ISI序列发生明显变化。     

脑深部电刺激猴帕金森病模型的建立

目的通过猴偏侧帕金森病（Parkinson disease,PD）模型丘脑底核（subthalamic nucleus,STN）脑深部电刺激（deep brain stimulation,DBS）系统的植入,对脑深部电刺激动物模型的制备进行了探讨.方法2只猴偏侧PD模型,按照猴脑立体定向图谱,在右侧STN植入脑深部刺激电极,并同期皮下植入脉冲发生器.术后行头颅X线平片和MRI检查,给予慢性高频电刺激,观察运动症状改善.结果2只偏侧猴PD模型成功的同期植入DBS系统,术后的症状观察和阿朴吗啡（apomorphine,APO）诱发旋转实验,证实STN慢性高频电刺激有效地缓解了猴PD样症状.结论通过立体定向技术同期将DBS系统植入动物体内,可以有效的建立DBS动物模型,为DBS在神经疾病的应用研究提供了良好的实验模型.     

运动障碍病的神经电生理基础

目的探讨运动障碍病的细胞学病理生理基础,提高手术治疗的有效率和安全性.方法回顾过去3年的工作,1200例运动障碍病患者接受了微电极导向的立体定向神经外科手术.包括帕金森性病(PD)、原发性震颤(ET)、扭转痉挛和痉挛性斜颈等.手术的靶点包括苍白球腹后部(PVP),丘脑底核(STN)和丘脑腹外侧核(VL).术中应用微电极和肌电(EMG)记录技术,采集GPi,STN和VL神经元和肢体肌电活动.术后应用分析软件甄别单细胞及其电活动特点,分析其与临床症状的关系,并进行相关性检验.结果PD性震颤在GPi,STN、VL获得相关神经元簇放电频率是不一致,可指导临床.原发性震颤在丘脑腹中间核(Vim)获取的放电频率,也有临床指导意义.扭转痉挛和痉挛性斜颈扭转痉挛和痉挛性斜颈患者的神经元簇放电无明显规则可寻.结论识别和确定GPi、STN和VL细胞电活动特点及其分布,对于指导立体定向手术的功能定位,提高运动障碍病手术治疗的疗效和降低手术并发症具有重要的意义.     

人用DBS系统在脑深部电刺激猴模型构建中的应用

目的探讨人用脑深部电刺激(DBS)系统在构建猴脑深部电刺激模型中的应用。方法 4只偏侧帕金森病(PD)猴模型,按照猴脑立体定向图谱,在右侧丘脑底核(STN)植入脑深部刺激电极(Medtronic 3389),其中刺激组2只猴同期皮下植入Medtronic 7495型连接导线和Soletra TM7426型脉冲发生器,术后一周给予慢性高频电刺激。另2只偏侧PD模型猴仅在右侧STN植入电极,不植入脉冲发生器,作为对照组。连续观察12个月,进行运动障碍评分观察和阿朴吗啡(APO)诱发旋转实验。结果术后影像学观察电极前端均位于STN核范围内;刺激组同期植入脉冲发生器给予慢性高频电刺激,猴偏侧帕金森样症状明显改善,有效高频电刺激可以立即停止APO所诱发的旋转,而对照组在观察期内症状无明显缓解。结论人用DBS系统通过立体定向技术植入猴脑内特定靶点,可以有效的建立DBS动物模型,为DBS在神经系统疾病中的应用研究提供了良好的实验模型。     

帕金森病患者僵直迟缓症状神经元电活动特点研究

目的探讨帕金森病(PD)患者僵直迟缓症状的神经元电活动特点。方法 25例僵直迟缓为主征的PD患者接受立体定向丘脑底核(STN)脑深部电极植入术(DBS)。术中通过微电极记录技术采集神经元电活动。应用单细胞分析方法,峰间隔分析方法分析神经元放电的频率和形式,应用功率谱分析方法分析神经元放电周期节律。结果分析了180个信号稳定的神经元,平均放电频率为(40.6±22.3)Hz;有35.6%(n=64)神经元有周期节律性放电,放电周期节律在β节律内。结论β节律的神经元周期节律性电活动可能和PD僵直迟缓症状的病理生理改变有关。     

微电极记录与影像技术联合应用对帕金森病脑深部电刺激最佳刺激治疗位置的研究

目的探讨帕金森病(PD)患者脑深部电刺激(DBS)术最佳刺激靶点的位置。方法 40例PD患者接受立体定向双侧丘脑底核(STN)脑深部电刺激术。术中通过微电极记录采集神经元电活动,埋置脑深部电刺激器,术后复查电极位置,通过影像资料和电生理数据,确定电极尖端坐标,并计算电极各触点坐标,以及电极针道中STN上下边界和中心点的坐标。结果最佳刺激触点中心坐标的平均位置与STN上边界坐标的平均位置的差异无统计学意义。结论 STN上边界区域为DBS治疗PD的最佳刺激位置。     

Intraocular co-grafts of fetal dorsal raphe nucleus and suprachiasmatic nucleus

Serotonergic neurons in the fetal dorsal raphe nucleus were grafted together with fetal anterior hypothalamic tissue including the suprachiasmatic nucleus (SCN) to the anterior eye chamber of adult rats. After 6 weeks transplantation, the double grafts were immunocytochemically examined using antisera against serotonin, arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP). The raphe grafts contained a large number of serotonin-immunoreactive neurons and fibers, but only a few AVP-immunoreactive fibers and VIP-immunoreactive neurons and fibers. On the other hand, numerous AVP- and VIP-immunoreactive neurons and fibers were found in the SCN of the anterior hypothalamic graft. Outgrowing serotonin-immunoreactive fibers from the raphe tissue were densely distributed in the anterior hypothalamic graft. In the SCN, however, only a few fibers were detected. The results demonstrate that the isolated anterior hypothalamic grafts can be innervated by the serotonergic neurons from the raphe grafts, but the innervation pattern of these fibers was quite different from the normal rat. The present results indicate that the isolated SCN has an inhibitory influence on the growth of serotonergic fibers.     

Intracellular study of nucleus parabrachialis and nucleus tractus solitarii interconnections

Responses of the nucleus parabrachialis (PBN) neurons to electrical stimulation of the nucleus tractus solitarii (NTS) were investigated by intracellular recording technique in anesthetized rats. Excitatory postsynaptic potentials (EPSPs) were evoked by ipsilateral NTS stimulation in 38 PBN neurons. They were considered monosynaptic because their latencies did not change with either variations in stimulus intensity or high-frequency repetitive stimulation. The latencies of EPSPs ranged from 1.2 to 6.9 ms. PBN neurons were also antidromically activated by NTS stimulation, giving a mean axonal conduction velocity of 4.6 m/s. Some of these neurons also responded with monosynaptic EPSPs to NTS stimulation. Direct stimulation of these neurons by depolarizing current pulses elicited repetitive firing with frequencies up to 350 Hz. The morphological analysis of 5 PBN neurons labeled with horseradish peroxidase (HRP) indicates that the soma were fusiform in shape, and the size varied from 163 to 783 microns 2. All neurons had 3-5 spiny primary dendrites which extended in a predominantly mediolateral direction. Axons arose from a proximal dendritic trunk, close to the soma. The results indicated that PBN is reciprocally connected with the NTS which elicits an excitatory effect on PBN neurons.     

Projections of the lateral reticular nucleus to the cochlear nucleus in rats

The lateral reticular nucleus (LRN) resides in the rostral medulla and caudal pons, is implicated in cardiovascular regulation and cranial nerve reflexes, and gives rise to mossy fibers in the cerebellum. Retrograde tracing data revealed that medium-sized multipolar cells from the magnocellular part of the LRN project to the cochlear nucleus (CN). We sought to characterize the LRN projection to the CN using BDA injections. Anterogradely labeled terminals in the ipsilateral CN appeared as boutons and mossy fibers, and were examined with light and electron microscopy. The terminal field in the CN was restricted to the granule cell domain (GCD), specifically in the superficial layer along the anteroventral CN and in the granule cell lamina. Electron microscopy showed that the smallest LRN boutons formed 1-3 synapses, and as boutons increased in size, they formed correspondingly more synapses. The largest boutons were indistinguishable from the smallest mossy fibers, and the largest mossy fiber exhibited 15 synapses. Synapses were asymmetric with round vesicles and formed against thin dendritic profiles characterized by plentiful microtubules and the presence of fine filopodial extensions that penetrated the ending. These structural features of the postsynaptic target are characteristic of the terminal dendritic claw of granule cells. LRN projections are consistent with known organizational principles of non-auditory inputs to the GCD.     

Direct catecholaminergic projection from nucleus tractus solitarii to supraoptic nucleus

To determine whether the supraoptic nucleus (SON) receives a direct projection from catecholamine cells of the nucleus tractus solitarii (NTS), retrograde transport of rhodamine-tagged latex microspheres was combined with a procedure for the fluorescence histochemical visualization of catecholamines. SON tracer injections, made via transpharyngeal approach, retrogradely labelled cells at all levels of NTS, although the majority were located caudal to obex with an ipsilateral predominance. Approximately half of these cells were also identified as catecholaminergic; the relatively caudal level in the dorsomedial medulla of most of these cells suggests that they probably correspond to the A2 catecholamine cell group.     

Synaptic distribution of afferents from reticular nucleus in ventroposterior nucleus of cat thalamus

This study was aimed at determining the synaptic circuitry that contributes to the alterations in thalamic function that accompany changes in behavioral states. The somatosensory sector of the thalamic reticular nucleus (RTN) was identified by microelectrode recording in cats and injected with Phaseolus vulgaris-leucoagglutinin (PHA-L). The axons of labeled RTN cells gave rise to collaterals within the RTN and continued into the dorsal thalamus where they terminated predominately in the ventral posterior lateral nucleus (VPL). After small injections in the upper limb representation of RTN, most labeled terminations in VPL were confined to its medial part, suggesting the presence of a topographic organization in the projection. Terminations were concentrated in localized, focal aggregations of boutons. Combined electron microscopic immunocytochemistry, using immunogold labeling for γ-aminobutyric acid (GABA), showed that the PHA-L labeled boutons were GABA-positive terminals that ended in symmetrical synapses. Eighty-two percent of these synapses were on dendrites of relay neurons, 8.5% on dendrites of interneurons, and 9.3% on somata. The terminals of RTN axons form the majority of axon terminals ending in symmetrical synapses in VPL. Their concentration on relay neurons probably underlies the capacity of the RTN projection to reduce background activity of VPL relay neurons in the awake state and to maintain oscillatory behavior of these neurons in drowsiness and early phases of Sleep. © 1995 Wiley-Liss, Inc.     

Types of neurons in nucleus gracilis and nucleus cuneatus of the European bison

The study was carried out on the medullae oblongatae of four European bisons. Preparations were made according to the Nissl, Klüver-Barrera and Golgi methods. Nucleus gracilis and nucleus cuneatus of the European bison are formed of 4 types of neurons. Type I--triangular cells. The perikaryon issues 3 dendrites bifurcating once or twice. The dendritic field is ball-shaped. A single thin axon emerges directly from the soma. Tiny granules of the tigroidal substance are very densely distributed and penetrate into the initial segments of dendrites. Type II--multipolar cells. These neurons have 7-9 thick dendrites which bifurcate twice. The dendritic field is ball-shaped. A single axon, 2 microns thick, emerges directly from the perikaryon. The cells contain thick spherical granules of the tigroidal substance. Type III--fusiform cells. From both poles of the perikaryon 2-3 thick dendrites originate which first bifurcate and next give off 2-3 branches. At each pole of the cell there is a separate dendritic field having a stream-like form. The axon arises from the lateral surface of the perikaryon. The tigroidal substance has a form of elongate bands. Type IV--rounded cells. Three thick dendrites are concentrated at one pole of the cell. The dendrites give off collaterals and ramify. The dendritic field has a stream-like form. The axon emerges from the perikaryon, a long distance from the dendrites. Thick granules of the tigroidal substance are evenly distributed in the cell.     

Dorsal nucleus of the lateral lemniscus: A nucleus of GABAergic projection neurons

Immunocytochemical staining of the dorsal nucleus of the lateral lemniscus with a well characterized antiserum to glutamate decarboxylase reveals that all, or nearly all, cells in this nucleus show immunoreactivity without the use of agents to block axonal transport. Most somata and dendrites are also contacted by immunoreactive axonal endings. It has previously been established that this nucleus is richly innervated by ascending lemniscal fibers and contains different types of neurons that project to the inferior colliculus. One may conclude that this precollicular nucleus is a major GABAergic feedforward inhibitory center in the acoustic pathway.     

The pedunculopontine tegmental nucleus issues collaterals to the fastigial nucleus and rostral ventrolateral reticular nucleus in the rat

The pedunculopontine-laterodorsal tegmental nuclear complex was identified as a major source of brainstem afferents terminating in the fastigial cerebellar nucleus and/or ventrolateral reticular nucleus (n.Rvl). Collaterals from the pedunculopontine nucleus (Ch5 area) to rostral [vasopressor] regions of the fastigial nucleus and ventral reticular formation were revealed with a combined retrograde tracing technique. The data implicate acetylcholine as a transmitter and raise the hypothesis that the identified afferents may contribute to the autonomic and behavioral responses to midline cerebellar stimulation.     

Basal interstitial nucleus of the cerebellum: cerebellar nucleus related to the flocculus

We have shown that the monkey flocculus is not connected with any of the major, well-demarcated cerebellar nuclei. There is, however, a broadly distributed interstitial population of neurons in the white matter ventral to the cerebellar nuclei and extending into the peduncle of the flocculus; this population, previously undescribed in the monkey, has reciprocal connections with the flocculus (Langer et al., '85a,b). Several lines of evidence indicate that this collection of neurons, called the basal interstitial nucleus of the cerebellum (BIN/Cb), can justifiably be considered a nucleus. (1) Injection of horseradish peroxidase (HRP) into the flocculus always labels a group of neurons that lie immediately ventral to the well-demarcated cerebellar nuclei and extend posteromedially into the lateral margin of the nodulus and rostrolaterally around the caudal surface of the y-group, infiltrating the peduncle of the flocculus. (2) In Nissl-stained material there is a readily seen collection of neurons that are clearly distinct from the overlying cerebellar nuclei, with precisely the same distribution. These neurons have a characteristic morphology: they are intermediate-sized, chromatophilic, multipolar, and fusiform, and have rapidly tapering proximal dendrites. The cell nucleus is generally placed eccentrically in the cell body, against the plasma membrane or in one pole of the cell. The Nissl substance is usually finely granular in the center of the cell body and forms dense clumps adjacent to the cell membrane. (3) Anterograde label from injections of HRP or tritiated amino acids into the flocculus extends over the same group of neurons. In one brain with an HRP injection involving a part of the BIN/Cb there was a patchy, clustered distribution of labeled Purkinje cells extending throughout the flocculus and into the adjacent lateral parts of the simple lobule. The clusters were confined to the medial half of many of the floccular folia.